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Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome
Journal Pre-proof Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome Keziban DOGAN, Caglar HELVACIOGLU, Sema BAGHAKI, Murat EKIN PII:
S1871-4021(20)30009-6
DOI:
https://doi.org/10.1016/j.dsx.2020.01.008
Reference:
DSX 1562
To appear in:
Diabetes & Metabolic Syndrome: Clinical Research & Reviews
Received Date: 25 September 2019 Revised Date:
16 January 2020
Accepted Date: 16 January 2020
Please cite this article as: DOGAN K, HELVACIOGLU C, BAGHAKI S, EKIN M, Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://doi.org/10.1016/ j.dsx.2020.01.008. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Ltd on behalf of Diabetes India.
Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome Running Head: Serum vaspin levels in women with PCOS Keziban DOGAN MD 1, Caglar HELVACIOGLU MD 1, Sema BAGHAKI MD 1, Murat EKIN MD 1 1
Department of Obstetrics and Gynecology, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital, Istanbul, Tukey
Corresponding author: Keziban DOGAN Tevfik Saglam Street, No: 11, Zuhuratbaba, Bakirkoy Istanbul, Turkey Phone: 0090 535 633 62 07 Fax: 0090 (212) 542 44 91 Email address: [email protected] Caglar HELVACIOGLU, MD Email address: [email protected] Sema BAGHAKI,MD Email address: [email protected] Murat EKIN, MD Email address: muratekinmd@ gmail.com
Keypoints This study showed that there is a positive correlation between serum Visceral Adipose tissue derived Serine Protease Inhibitor (VASPIN) level and polycystic ovary syndrome (PCOS). In previous studies, this relation was attributed to the generalization of higher amount of adipose tissue in patients with PCOS. However, we detected that VASPIN is significantly high in patients with PCOS regardless of BMI. We also showed that metabolic parameters such as fasting insulin, HOMA-IR, triglycerides and LDL-C levels were increased in lean women with PCOS.
Introduction PCOS affects 5-10% of women in reproductive age. The clinical presentations of PCOS may consist of irregular menstruation, hirsutism, insulin resistance causing glucose intolerance or diabetes mellitus and dyslipidemia (1,2). It is known that 40-85% of patients with PCOS are overweight or obese (3,4). Visceral adipose tissue derived serine protease inhibitor (VASPIN) is secreted from adipose tissue and has an important function in endogenous glucose regulation by inhibiting serine protease (5,6). In the recent studies, it is found that elevated levels of vaspin is associated with obesity, impaired insulin sensitivity, and type 2 diabetes in humans (7,8). However, the relationship between vaspin and PCOS has not yet established well. Some studies found a positive correlation between PCOS and serum vaspin levels whereas others found no significant relation (9-11). In this study, we aimed to investigate serum vaspin levels in non-obese, overweight and obese women with PCOS and to compare them with control groups without PCOS. Furthermore, we analyzed anthropometric measurements as well as lipidemic and glycemic parameters in both groups. Material and Methods We conducted this cross-sectional, case-control study in the Obstetrics and Gynecology Department, University of Health Sciences Hospital in Istanbul between 2014 and 2016. Rotterdam 2003 criteria were used for the diagnosis of PCOS (13,14). BMI of 25 to 29.9 kg/m2 is defined as overweight and BMI of >30 kg/m2 is considered as obese. The waist-tohip ratio (WHR) was measured and recorded. Patients with endocrinological disorders or the patients who use any medicines are excluded. All blood samples were taken in the morning after 12-hour fasting. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free
testosterone, fasting insulin and glucose level, triglycerides, high-density lipoprotein
cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. AU 5800 autoanalyzer and Beckman Coulter marker kits were used for the spectrophotometrical analysis of biochemical tests. Homeostatic model assessment for insulin resistance (HOMAIR) is used to measure insulin resistance [15].
Plasma fraction was removed after
centrifugation for 10 minutes at 3000 x rpm and they were maintained at -80°C before performing assays for vaspin analysis. Vaspin levels were measured by using ELISA kit (Hangzhou Eastbiopharm Co., Ltd, Shangai). The detection range of the kit was 0.2-9.4 ng/ml. We used the Number Cruncher Statistical System 2007 (Kaysville, Utah, USA) statistical software for the statistical analyses. Student’s t-test, the Mann–Whitney U test, the Kruskal– Wallis tests were used. Receiver operating characteristic (ROC) curve analysis and diagnostic screening tests including sensitivity, specificity, and positive and negative predictive value were used to determine the cut-off point of vaspin measurements. The confidence interval of 95% is determined to evaluate results and a p-value <0.05 was considered significant.
Results The study population (n=140) consisted of non-obese (n=28), overweight (n=26), and obese (n=24) women with PCOS, and a control group including non-obese (n=28), overweight (n=18), and obese (n=16) women. The mean age of the groups was 24.9±5.8 years. As shown in Table 1, there were statistically significant differences in WHR, fasting insulin level, HOMA-IR, LH/FSH ratio, free testosterone, triglycerides, LDL-C, Ferriman–Gallwey scores and vaspin levels between the lean groups. The odds ratio (OR) for vaspin cut-off value of 2.08 was 13.8. We also observed significant differences for WHR, LH/FSH ratio, LDL-C, Ferriman–Gallwey scores and vaspin levels between overweight groups. The risk of PCOS in patients with vaspin levels of 2.21 and above was 14.7 times higher (OR: 14.7) than control group. There were significant differences in LH/FSH, free testosteron, Ferriman–Gallwey scores and vaspin levels in the obese groups. OR for vaspin cut-off value of 2.88 was 11.6. We found no significant increase in vaspin levels in both the PCOS and control groups as BMI increases (p>0.05).
Discussion The most prominent result of our study is that serum vaspin levels were significantly higher in women with PCOS. Similarly, Tan et al. detected that obese women with PCOS had enhanced vaspin mRNA expression and protein in omental adipose tissue. They also found high plasma HOMA- IR and glucose levels suggesting that high vaspin levels might be a consequence of insulin resistance (18). Koiou et al. found higher levels of vaspin in both lean and obese patients with PCOS than control group. The quantitative insulin sensitivity check index was
lower in women with PCOS, and the authors deducted that insulin resistance and obesity stimulated vaspin levels (10). Moreover, Hida et al. found that obesity and insulin resistance caused increased vaspin in Otsuka Long Evans Tokushima Fatty rats (5). Since vaspin is secreted from adipose tissue, the levels of vaspin are expected to increase as BMI increases. However, we found no significant increase in vaspin levels of PCOS and control groups despite the increase in BMI was significantly higher in women with PCOS compared to control group. According to our study results, we suggest that there might be a closer relation between vaspin and PCOS than vaspin and BMI. These data also intrigue that vaspin may be elevated by a different mechanism other than being secreted from fat tissue in patients with PCOS. Taking all together, molecular studies to identify the exact physiologic pathway between vaspin, adipose tissue, insulin resistance in women with PCOS are needed to confirm these findings. The major limitation of our study is that BMI was the only indicator of fat tissue, we did not specifically measure the amount of fat by using dedicated devices. In conclusion; considering the difficulties in diagnosing PCOS, the results of our study suggest that serum vaspin levels may be a novel marker in the diagnosis of PCOS in women regardless of BMI.
Disclosure The authors received no specific funding for this work. References 1.
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and
implication for pathogenesis. Endocr Rev 1997; 18: 774-800.
2.
Wild RA, Painter RD, Coulson PB, et al: Lipoprotein lipid concentrations and
cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab1985; 61:946–951, 3.
Diamanti-Kandarakis E, Kandaraki E, Christakou C, Panidis D The effect of
pharmaceutical intervention on lipid profile in polycystic ovary syndrome. Obes Rev 2009; 10: 431-441.
4.
Randeva HS, Tan BK,Weickert MO, et al.Cardiometabolic aspects of the polycystic
ovary syndrome. Endocr Rev 2012;33:812.
5.
Hida K, Wada J, Eguchi J, et al: Visceral adipose tissue-derived serine protease
inhibitor: a unique insulin-sensitizing adipocytokine in obesity. PNAS 2005 102 10610– 10615.
6.
Wada J. Vaspin: a novel serpin with insulin-sensitizing effects. Expert Opinion on
Investigational Drugs 2008; 17: 327–333.
7.
Kloting N, Berndt J, Kralisch S, et al: Vaspin gene expression in human adipose
tissue: association with
obesity and type 2 diabetes. Biochem Biophys Res Commun
2006;339: 430-436.
8.
Youn BS, Klöting N, Kratzsch J, t al: Serum vaspin concentrations in human
obesity and type 2 diabetes. Diabetes 2008; 57: 372377.
9.
Cakal E, Ustun Y, Engin-Ustun Y, t al: Serum vaspin and C-reactive protein levels
with polycystic ovaries and polycystic ovary syndrome. Gynecol Endocrinol. 2011; 27 :491-5
10.
Koiou E, Tziomalos K, Dinas K, et al. The effect of weight loss and treatment with
metformin on serum vaspin levels in women with polycystic ovary syndrome. Endocr J. 2011;58:237-46.
11. Akbarzadeh S, Ghasemi S, Kalantarhormozi M,
et al. Relationship among plasma
adipokines, insulin and androgens level as well as glycemic and lipidemic markers with the incidence of PCOS in women with normal BMI. Gynecol Endocrinol. 2012; 28: 521-4.
12. Mahde A, Shaker M, Al-Mashhadani Z. Study of Omentin1 and Other Adipokines and Hormones in PCOS Patients. Oman Med J. 2009; 24:108-18.
13. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group; Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004: 19: 41-47.
14. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440–1447.
15. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.
16. Rocha MP, Marcondes JA, Barcellos CR, et al: Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern, and predictors. Gynecol Endocrinol. 2011;27:814-9.
17. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 2002;13:84–89.
18.
Tan BK, Heutling D, Chen J, et al: Metformin decreases the adipokine vaspin in
overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes. 2008;57:1501– 1507
Grup I ( BMI: 18-24.9) Control (n=28)
Age (years)
BMI (kg/m2)
Waist-tohip ratio Fasting insulin level (µIU/mL)
PCOS (n=28)
Min-Max
Min-Max
Min-Max
Mean±SD(Media n)
Mean±SD(Media n)
Mean±SD(Media n)
18-30
18-32
18-39
19-36
21-38
17-33
a
28.25±5.82 (28)
21.64±3.75 (20)
18.08-24.61
18.37-24.84 a
20.63±1.61 (20.7)
21.70±1.72 (21.5)
0.69-0.77
0.69-0.79 a
0.73±0.02 (0.7)
0.80±0.08 (0.8)
5.07.2022
1.02.1971 b
(mg/dl)
88.50±10.6 (87)
1.10-5.32
0.25-17.35
a
b
HOMA-IR 2.31±1.04 (2)
4.64±4.24 (3.5)
0.45-1.08
0.85-4.71 b
0.80±0.15 (0.8)
1.85±0.99 (1.3)
0.20-2.45
0.88-6.30 b
1.09±0.67 (1)
130.57±63.78 (126.5)
42-66 55.21±7.54 (56.5)
51.29±12.94 (51.5)
62-128
56-178
85.93±19.73 (82)
107.14±30.87 (101)
Mar.15
Şub.14
7.18±2.67 (7)
9.75±2.74 (9)
0.14-3.86
0.61-7.54
1.42±0.85 (1.38)
3.38±1.72 (3.2)
b
a
0.006*
b
Mann Whitney U test
25.39-28.52
25.26-29.75 a
27.09±1.05 (27.5)
27.31±1.31 (27.4)
0.74-0.80
0.72-0.94 a
0.77±0.02 (0.8)
0.81±0.06 (0.8)
5.7-23.4
2.4-58.5 b
15.64±4.58 (17.3)
24.06±14.92 (17.6)
71-103
69-111 a
0.265 92.00±9.45 (95.5)
91.92±10.71 (91.5)
1.07-5.03
0.56-15.41 b
0.010* 3.61±1.21 (3.9)
5.63±3.92 (4.2)
0.40-0.87
1.00-3.89 b
0.001* 0.76±0.12 (0.8)
2.05±0.89 (1.7)
0.54-3.06
0.32-6.66 b
0.001*
0.017*
1.98±0.75 (2.1)
2.91±1.64 (2.4)
71-188
52-277 b
119.56±41.32 (108)
144.04±65.33 (124)
38-65
32-90 b
0.113 49.72±9.27 (47)
46.65±13.25 (44)
62-122
77-172
0.004*
0.001*
b
Student t Test
23.77±3.79 (23)
0.001*
32-85 b
27.72±5.57 (27)
0.020*
45-266 b
a
0.001*
3.04±1.39 (2.7)
64-185 Triglycerid e (mg/dl) 91.68±32.58 (82)
a
PCOS (n=24)
Mean±SD(Media n)
85.39±10.06 (84.5)
VASPIN (ng/ml)
Control (n=16)
Min-Max
63-109
FerrimanGallwey score
p
Min-Max
67-102
LDL-C (mg/dl)
PCOS (n=26)
Mean±SD(Media n)
Fasting glucose level
HDL–C (mg/dl)
Control (n=18)
Mean±SD(Media n)
10.73±3.93 (9.5)
Free Testostero n (ng/mL)
p
Grup I ( BMI: ≥30 )
Min-Max
20.16±16.28 (15.6)
LH/FSH ratio
Grup II ( BMI: 25-29.9)
94.33±17.94 (98)
118.62±26.34 (114)
3.Ara
Haz.17
7.56±2.20 (8)
10.62±3.10 (10.5)
0.27-2.28
0.68-6.99
0.001* 1.61±0.81 (1.5) *
3.09±1.28 (3.0)
b
a
b
0.008*
29.38±5.25 (29.5)
24.54±5.04 (24)
30.08-39.08
30.12-46.87
0.567 33.11±2.68 (32.7)
34.7±4.88 (33)
0.72-0.94
0.73-0.93
0.81±0.05 (0.8)
0.81±0.05 (0.8)
9.06.1986
9.9-157.3
27.5±20.21 (22.6)
40.23±30.85 (31.1)
76-166
67-114
0.003*
0.155
0.981 96.19±8.84 (98.5)
95.42±13.32 (96)
1.84-18.48
1.86-31.46
6.64±4.91 (5.5)
9.73±7.06 (7.3)
0.44-0.92
1.06-4.63
0.72±0.14 (0.7)
1.94±0.77 (1.9)
0.82-6.27
1.34-7.95
2.77±1.56 (2.4)
3.9±1.76 (3.7)
55-276
66-258
138±58.56 (137)
167±69.63 (161.5)
32-64
18-65
46.25±9.49 (45.5)
43.71±9.9 (43)
68-171
42-178
113.56±27.61 (113)
127.46±33.96 (124)
Mar.17
Mar.21
8.38±3.69 (7.5)
11.54±4.19 (12.5)
0.13-3.06
0.52-7.24
1.78±0.96 (1.96)
3.43±1.48 (3.23)
0.252
0.001*
0.073
0.322
0.201
0.004*
0.001*
0.001* *
p
a
0.006*
a
0.195
a
0.941
b
0.143
a
0.827
b
0.214
b
0.001*
b
0.036*
b
0.190
b
0.571
b
0.136
a
0.019*
b 0.001* *
significance level of *p<0,05, **p<0,01
BMI: body mass index, HOMA-IR: homeostatic model assessment for insulin resistance, FSH:follicle stimulating hormone, LH: luteinizing hormone, DHEA-SO4: dehydroepiandrosterone sulfate, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol
Tablo: 1 Characteristics of the study groups
CONFLICT OF INTEREST
The authors have no conflict of interest to disclose.
S1871-4021(20)30009-6
DOI:
https://doi.org/10.1016/j.dsx.2020.01.008
Reference:
DSX 1562
To appear in:
Diabetes & Metabolic Syndrome: Clinical Research & Reviews
Received Date: 25 September 2019 Revised Date:
16 January 2020
Accepted Date: 16 January 2020
Please cite this article as: DOGAN K, HELVACIOGLU C, BAGHAKI S, EKIN M, Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://doi.org/10.1016/ j.dsx.2020.01.008. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Ltd on behalf of Diabetes India.
Comparison of body mass index and metabolic parameters with serum vaspin levels in women with polycystic ovary syndrome Running Head: Serum vaspin levels in women with PCOS Keziban DOGAN MD 1, Caglar HELVACIOGLU MD 1, Sema BAGHAKI MD 1, Murat EKIN MD 1 1
Department of Obstetrics and Gynecology, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital, Istanbul, Tukey
Corresponding author: Keziban DOGAN Tevfik Saglam Street, No: 11, Zuhuratbaba, Bakirkoy Istanbul, Turkey Phone: 0090 535 633 62 07 Fax: 0090 (212) 542 44 91 Email address: [email protected] Caglar HELVACIOGLU, MD Email address: [email protected] Sema BAGHAKI,MD Email address: [email protected] Murat EKIN, MD Email address: muratekinmd@ gmail.com
Keypoints This study showed that there is a positive correlation between serum Visceral Adipose tissue derived Serine Protease Inhibitor (VASPIN) level and polycystic ovary syndrome (PCOS). In previous studies, this relation was attributed to the generalization of higher amount of adipose tissue in patients with PCOS. However, we detected that VASPIN is significantly high in patients with PCOS regardless of BMI. We also showed that metabolic parameters such as fasting insulin, HOMA-IR, triglycerides and LDL-C levels were increased in lean women with PCOS.
Introduction PCOS affects 5-10% of women in reproductive age. The clinical presentations of PCOS may consist of irregular menstruation, hirsutism, insulin resistance causing glucose intolerance or diabetes mellitus and dyslipidemia (1,2). It is known that 40-85% of patients with PCOS are overweight or obese (3,4). Visceral adipose tissue derived serine protease inhibitor (VASPIN) is secreted from adipose tissue and has an important function in endogenous glucose regulation by inhibiting serine protease (5,6). In the recent studies, it is found that elevated levels of vaspin is associated with obesity, impaired insulin sensitivity, and type 2 diabetes in humans (7,8). However, the relationship between vaspin and PCOS has not yet established well. Some studies found a positive correlation between PCOS and serum vaspin levels whereas others found no significant relation (9-11). In this study, we aimed to investigate serum vaspin levels in non-obese, overweight and obese women with PCOS and to compare them with control groups without PCOS. Furthermore, we analyzed anthropometric measurements as well as lipidemic and glycemic parameters in both groups. Material and Methods We conducted this cross-sectional, case-control study in the Obstetrics and Gynecology Department, University of Health Sciences Hospital in Istanbul between 2014 and 2016. Rotterdam 2003 criteria were used for the diagnosis of PCOS (13,14). BMI of 25 to 29.9 kg/m2 is defined as overweight and BMI of >30 kg/m2 is considered as obese. The waist-tohip ratio (WHR) was measured and recorded. Patients with endocrinological disorders or the patients who use any medicines are excluded. All blood samples were taken in the morning after 12-hour fasting. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free
testosterone, fasting insulin and glucose level, triglycerides, high-density lipoprotein
cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. AU 5800 autoanalyzer and Beckman Coulter marker kits were used for the spectrophotometrical analysis of biochemical tests. Homeostatic model assessment for insulin resistance (HOMAIR) is used to measure insulin resistance [15].
Plasma fraction was removed after
centrifugation for 10 minutes at 3000 x rpm and they were maintained at -80°C before performing assays for vaspin analysis. Vaspin levels were measured by using ELISA kit (Hangzhou Eastbiopharm Co., Ltd, Shangai). The detection range of the kit was 0.2-9.4 ng/ml. We used the Number Cruncher Statistical System 2007 (Kaysville, Utah, USA) statistical software for the statistical analyses. Student’s t-test, the Mann–Whitney U test, the Kruskal– Wallis tests were used. Receiver operating characteristic (ROC) curve analysis and diagnostic screening tests including sensitivity, specificity, and positive and negative predictive value were used to determine the cut-off point of vaspin measurements. The confidence interval of 95% is determined to evaluate results and a p-value <0.05 was considered significant.
Results The study population (n=140) consisted of non-obese (n=28), overweight (n=26), and obese (n=24) women with PCOS, and a control group including non-obese (n=28), overweight (n=18), and obese (n=16) women. The mean age of the groups was 24.9±5.8 years. As shown in Table 1, there were statistically significant differences in WHR, fasting insulin level, HOMA-IR, LH/FSH ratio, free testosterone, triglycerides, LDL-C, Ferriman–Gallwey scores and vaspin levels between the lean groups. The odds ratio (OR) for vaspin cut-off value of 2.08 was 13.8. We also observed significant differences for WHR, LH/FSH ratio, LDL-C, Ferriman–Gallwey scores and vaspin levels between overweight groups. The risk of PCOS in patients with vaspin levels of 2.21 and above was 14.7 times higher (OR: 14.7) than control group. There were significant differences in LH/FSH, free testosteron, Ferriman–Gallwey scores and vaspin levels in the obese groups. OR for vaspin cut-off value of 2.88 was 11.6. We found no significant increase in vaspin levels in both the PCOS and control groups as BMI increases (p>0.05).
Discussion The most prominent result of our study is that serum vaspin levels were significantly higher in women with PCOS. Similarly, Tan et al. detected that obese women with PCOS had enhanced vaspin mRNA expression and protein in omental adipose tissue. They also found high plasma HOMA- IR and glucose levels suggesting that high vaspin levels might be a consequence of insulin resistance (18). Koiou et al. found higher levels of vaspin in both lean and obese patients with PCOS than control group. The quantitative insulin sensitivity check index was
lower in women with PCOS, and the authors deducted that insulin resistance and obesity stimulated vaspin levels (10). Moreover, Hida et al. found that obesity and insulin resistance caused increased vaspin in Otsuka Long Evans Tokushima Fatty rats (5). Since vaspin is secreted from adipose tissue, the levels of vaspin are expected to increase as BMI increases. However, we found no significant increase in vaspin levels of PCOS and control groups despite the increase in BMI was significantly higher in women with PCOS compared to control group. According to our study results, we suggest that there might be a closer relation between vaspin and PCOS than vaspin and BMI. These data also intrigue that vaspin may be elevated by a different mechanism other than being secreted from fat tissue in patients with PCOS. Taking all together, molecular studies to identify the exact physiologic pathway between vaspin, adipose tissue, insulin resistance in women with PCOS are needed to confirm these findings. The major limitation of our study is that BMI was the only indicator of fat tissue, we did not specifically measure the amount of fat by using dedicated devices. In conclusion; considering the difficulties in diagnosing PCOS, the results of our study suggest that serum vaspin levels may be a novel marker in the diagnosis of PCOS in women regardless of BMI.
Disclosure The authors received no specific funding for this work. References 1.
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and
implication for pathogenesis. Endocr Rev 1997; 18: 774-800.
2.
Wild RA, Painter RD, Coulson PB, et al: Lipoprotein lipid concentrations and
cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab1985; 61:946–951, 3.
Diamanti-Kandarakis E, Kandaraki E, Christakou C, Panidis D The effect of
pharmaceutical intervention on lipid profile in polycystic ovary syndrome. Obes Rev 2009; 10: 431-441.
4.
Randeva HS, Tan BK,Weickert MO, et al.Cardiometabolic aspects of the polycystic
ovary syndrome. Endocr Rev 2012;33:812.
5.
Hida K, Wada J, Eguchi J, et al: Visceral adipose tissue-derived serine protease
inhibitor: a unique insulin-sensitizing adipocytokine in obesity. PNAS 2005 102 10610– 10615.
6.
Wada J. Vaspin: a novel serpin with insulin-sensitizing effects. Expert Opinion on
Investigational Drugs 2008; 17: 327–333.
7.
Kloting N, Berndt J, Kralisch S, et al: Vaspin gene expression in human adipose
tissue: association with
obesity and type 2 diabetes. Biochem Biophys Res Commun
2006;339: 430-436.
8.
Youn BS, Klöting N, Kratzsch J, t al: Serum vaspin concentrations in human
obesity and type 2 diabetes. Diabetes 2008; 57: 372377.
9.
Cakal E, Ustun Y, Engin-Ustun Y, t al: Serum vaspin and C-reactive protein levels
with polycystic ovaries and polycystic ovary syndrome. Gynecol Endocrinol. 2011; 27 :491-5
10.
Koiou E, Tziomalos K, Dinas K, et al. The effect of weight loss and treatment with
metformin on serum vaspin levels in women with polycystic ovary syndrome. Endocr J. 2011;58:237-46.
11. Akbarzadeh S, Ghasemi S, Kalantarhormozi M,
et al. Relationship among plasma
adipokines, insulin and androgens level as well as glycemic and lipidemic markers with the incidence of PCOS in women with normal BMI. Gynecol Endocrinol. 2012; 28: 521-4.
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Grup I ( BMI: 18-24.9) Control (n=28)
Age (years)
BMI (kg/m2)
Waist-tohip ratio Fasting insulin level (µIU/mL)
PCOS (n=28)
Min-Max
Min-Max
Min-Max
Mean±SD(Media n)
Mean±SD(Media n)
Mean±SD(Media n)
18-30
18-32
18-39
19-36
21-38
17-33
a
28.25±5.82 (28)
21.64±3.75 (20)
18.08-24.61
18.37-24.84 a
20.63±1.61 (20.7)
21.70±1.72 (21.5)
0.69-0.77
0.69-0.79 a
0.73±0.02 (0.7)
0.80±0.08 (0.8)
5.07.2022
1.02.1971 b
(mg/dl)
88.50±10.6 (87)
1.10-5.32
0.25-17.35
a
b
HOMA-IR 2.31±1.04 (2)
4.64±4.24 (3.5)
0.45-1.08
0.85-4.71 b
0.80±0.15 (0.8)
1.85±0.99 (1.3)
0.20-2.45
0.88-6.30 b
1.09±0.67 (1)
130.57±63.78 (126.5)
42-66 55.21±7.54 (56.5)
51.29±12.94 (51.5)
62-128
56-178
85.93±19.73 (82)
107.14±30.87 (101)
Mar.15
Şub.14
7.18±2.67 (7)
9.75±2.74 (9)
0.14-3.86
0.61-7.54
1.42±0.85 (1.38)
3.38±1.72 (3.2)
b
a
0.006*
b
Mann Whitney U test
25.39-28.52
25.26-29.75 a
27.09±1.05 (27.5)
27.31±1.31 (27.4)
0.74-0.80
0.72-0.94 a
0.77±0.02 (0.8)
0.81±0.06 (0.8)
5.7-23.4
2.4-58.5 b
15.64±4.58 (17.3)
24.06±14.92 (17.6)
71-103
69-111 a
0.265 92.00±9.45 (95.5)
91.92±10.71 (91.5)
1.07-5.03
0.56-15.41 b
0.010* 3.61±1.21 (3.9)
5.63±3.92 (4.2)
0.40-0.87
1.00-3.89 b
0.001* 0.76±0.12 (0.8)
2.05±0.89 (1.7)
0.54-3.06
0.32-6.66 b
0.001*
0.017*
1.98±0.75 (2.1)
2.91±1.64 (2.4)
71-188
52-277 b
119.56±41.32 (108)
144.04±65.33 (124)
38-65
32-90 b
0.113 49.72±9.27 (47)
46.65±13.25 (44)
62-122
77-172
0.004*
0.001*
b
Student t Test
23.77±3.79 (23)
0.001*
32-85 b
27.72±5.57 (27)
0.020*
45-266 b
a
0.001*
3.04±1.39 (2.7)
64-185 Triglycerid e (mg/dl) 91.68±32.58 (82)
a
PCOS (n=24)
Mean±SD(Media n)
85.39±10.06 (84.5)
VASPIN (ng/ml)
Control (n=16)
Min-Max
63-109
FerrimanGallwey score
p
Min-Max
67-102
LDL-C (mg/dl)
PCOS (n=26)
Mean±SD(Media n)
Fasting glucose level
HDL–C (mg/dl)
Control (n=18)
Mean±SD(Media n)
10.73±3.93 (9.5)
Free Testostero n (ng/mL)
p
Grup I ( BMI: ≥30 )
Min-Max
20.16±16.28 (15.6)
LH/FSH ratio
Grup II ( BMI: 25-29.9)
94.33±17.94 (98)
118.62±26.34 (114)
3.Ara
Haz.17
7.56±2.20 (8)
10.62±3.10 (10.5)
0.27-2.28
0.68-6.99
0.001* 1.61±0.81 (1.5) *
3.09±1.28 (3.0)
b
a
b
0.008*
29.38±5.25 (29.5)
24.54±5.04 (24)
30.08-39.08
30.12-46.87
0.567 33.11±2.68 (32.7)
34.7±4.88 (33)
0.72-0.94
0.73-0.93
0.81±0.05 (0.8)
0.81±0.05 (0.8)
9.06.1986
9.9-157.3
27.5±20.21 (22.6)
40.23±30.85 (31.1)
76-166
67-114
0.003*
0.155
0.981 96.19±8.84 (98.5)
95.42±13.32 (96)
1.84-18.48
1.86-31.46
6.64±4.91 (5.5)
9.73±7.06 (7.3)
0.44-0.92
1.06-4.63
0.72±0.14 (0.7)
1.94±0.77 (1.9)
0.82-6.27
1.34-7.95
2.77±1.56 (2.4)
3.9±1.76 (3.7)
55-276
66-258
138±58.56 (137)
167±69.63 (161.5)
32-64
18-65
46.25±9.49 (45.5)
43.71±9.9 (43)
68-171
42-178
113.56±27.61 (113)
127.46±33.96 (124)
Mar.17
Mar.21
8.38±3.69 (7.5)
11.54±4.19 (12.5)
0.13-3.06
0.52-7.24
1.78±0.96 (1.96)
3.43±1.48 (3.23)
0.252
0.001*
0.073
0.322
0.201
0.004*
0.001*
0.001* *
p
a
0.006*
a
0.195
a
0.941
b
0.143
a
0.827
b
0.214
b
0.001*
b
0.036*
b
0.190
b
0.571
b
0.136
a
0.019*
b 0.001* *
significance level of *p<0,05, **p<0,01
BMI: body mass index, HOMA-IR: homeostatic model assessment for insulin resistance, FSH:follicle stimulating hormone, LH: luteinizing hormone, DHEA-SO4: dehydroepiandrosterone sulfate, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol
Tablo: 1 Characteristics of the study groups
CONFLICT OF INTEREST
The authors have no conflict of interest to disclose.